Comparison of the effects of aminoguanidine and L-carnitine treatments on somatosensorial evoked potentials in alloxan-diabetic rats

The effects of aminoguanidine (AG) and L-carnitine (LC) on somatosensorial evoked potential (SEP) latency and neural levels of thiobarbituric acid reactive substances (TBARS), products of lipid peroxidation, were compared in alloxan-diabetic rats. AG and LC were given to diabetic rats starting from the 3rd week after the induction of diabetes and lasting for 4 weeks. SEP latency was measured by stimulating via caudal nerve and recording via cortex, once weekly during the treatments. Diabetes caused deficits in SEP (P < 0.05 vs non-diabetic control rats, respectively). AG and LC restored SEP latencies slightly but not significantly, with the exception of the prominent effect of AG at the first week and both treatments at the 4th week of the treatments (P < 0.05 vs untreated diabetic rats, respectively). Diabetes caused elevation in neural TBARS levels (P < 0.05 vs non-diabetic group), which was prevented by both AG and LC (P < 0.05 vs untreated diabetic rats, respectively). Weight and the glucose levels were not influenced by the treatments. Our results suggest that AG improves SEP latencies better than LC. Our results also suggest that the beneficial effects of both AG and LC on diabetic neuropathy are not associated with the regulation of glycemia, but these effects may be related in part with prevention of lipid peroxidation.     

Effect of lithium on gastro-intestinal complications in alloxan-diabetic rats.

1. Decreased beta-adrenergic and serotonergic responses have been reported in gastro-intestinal tract of experimentally diabetic rats. Effects of lithium on the decreased beta-adrenergic and serotonergic responsiveness of the gastro-intestinal tract due to diabetes were investigated using gastric fundus strips and proximal duodenum from alloxan diabetic rats. 2. A 6-day treatment with lithium chloride (2 mEq/kg i.p. in saline) normalized the decreased gastro-intestinal responses of the alloxan-diabetic rats, whereas the lithium treatment did not affect the elevated blood glucose levels due to experimental diabetes. 3. Furthermore, the lithium treatments of control and alloxan-diabetic rats did not alter the relaxing effect of manganese chloride on the isolated duodenum. 4. These results strongly suggest that the improving effect of lithium is not related to adenylate cyclase activation and may be as a consequence of its direct action on the diabetic gastro-intestinal smooth muscles.     

Inhibitory role of Syzygium cumini on autacoid-induced inflammation in rats

The ethanolic extract of Syzygium cumini bark has been reported to possess anti-inflammatory activity in our previous studies. The present study is an attempt to elucidate the anti-inflammatory activity of S. Cumini bark against inflammation induced by individual autacoid insult. Histamine (1 mg/ml), 5-HT (1 mg/ml), bradykinin (0.02 mg/ml) and PGE2 (0.001 mg/ml) were used as inflammogens. One of these agents (0.1 ml) was injected s.c. into the right hind paw of each rat. The ethanolic extract of S. cumini bark was tested at the doses of 100, 300 and 1000 mg/kg, p.o. The results indicated the anti-inflammatory activity of S. cumini bark in histamine, 5-HT and PGE2-induced rat paw oedema. However, there was no such significant inhibition of oedema volume observed in bradykinin-induced rat paw oedema at any dose level. Thus, it is concluded that S. cumini exhibits inhibitory role on inflammatory response to histamine, 5-HT and PGE2.     

Antidiabetic activity of Bauhinia forficata extracts in alloxan-diabetic rats

The antidiabetic activity of aqueous, ethanolic and hexanic extracts of Bauhinia forficata was investigated in a model of alloxan-induced diabetes in rats. The biochemical parameters studied were: plasma glucose, serum triglycerides, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL). Extracts were administered daily for 7 d at doses of 200 and 400 mg/kg, p.o., 48 h after alloxan injection (60 mg/kg, i.v.). The alloxan-diabetic rats showed significant reductions in plasma glucose, triglycerides, total cholesterol and HDL-cholesterol after treatment with the extracts and glibenclamide (used as standard) as compared to the diabetic controls. Levels of LDL were not altered. In conclusion, our results showed that the plant extracts when administered by gavage may reduce glucose, triglycerides, total cholesterol and HDL-cholesterol levels. These results suggest the validity of the clinical use of B. forficata in the treatment of diabetes mellitus type II.     

The effects of a polychlorinated biphenyl mixture (Aroclor 1254) on liver gluconeogenic enzymes of normal and alloxan-diabetic rats.

Normal and alloxan-diabetic rats were fed ground Purina Laboratory Chow with or without 500 ppm of Aroclor 1254 (AR) ad lib for 2 weeks. In both normal and diabetic rats, AR administration decreased food consumption, weight gain and blood glucose concentration, and increased liver weight, liver:body weight ratio, total liver lipid, liver protein and malic enzyme (ME) activity. In the normal rat, AR increased the concentrations of acetoacetate and beta-hydroxybutyrate in blood, but in the diabetic rat the concentrations were markedly reduced. AR administration decreased the activity of phosphoenolpyruvate carboxykinase (PEPck) in normal liver and the activities of pyruvate carboxylase (PC), PEPck and glucose-6-phosphatase (G6Pase) in diabetic liver.     

Aldose reductase inhibitor zopolrestat restores allergic hyporesponsiveness in alloxan-diabetic rats

This study was undertaken to investigate the role of the aldose reductase in the refractoriness of diabetic rats to allergic inflammation. Wistar rats were actively sensitized with a mixture of Al(OH)3 plus ovalbumin and intrapleurally challenged with ovalbumin, 14 days later. Diabetes was induced by intravenous injection of alloxan into fasted rats, 7 days before sensitization, and the aldose reductase inhibitor zopolrestat was administered after 3 days of diabetes induction, once a day during 18 consecutive days. The treatment with zopolrestat restored antigen-induced protein extravazation and mast cell degranulation in the pleural cavity of diabetic sensitized rats. Zopolrestat also significantly reversed the suppression in the increase of total and specific levels of serum immunoglobulin E (IgE) noted in sensitized animals under conditions of diabetes. In addition, we noted that the drop in the pleural mast cell numbers as well as the increase in serum corticosterone levels in diabetic rats were inhibited by the drug. Our findings show that zopolrestat restored the hyporesponsiveness of diabetic rats to antigen provocation, in parallel with impairment of alloxan-induced mast cell depletion and hypercorticolism, indicating that polyol pathway activity seems to play an important role in these phenomena.     

Systemic anaphylaxis is prevented in alloxan-diabetic rats by a mechanism dependent on glucocorticoids

This study was undertaken to examine whether glucocorticoids could be implicated in the hyporesponsiveness of diabetic rats to systemic anaphylaxis. Rats were actively sensitized with a mixture of Al(OH)(3) plus ovalbumin and challenged i.v. with ovalbumin 14 days later. Diabetes was induced by alloxan-injected i.v. either before or after sensitization. Elevation of total and specific serum immunoglobulin E (IgE) was abolished in rats turned diabetic and then sensitised, but not in those first sensitised and then turned diabetic. In both conditions, increased serum corticosterone levels occurred in parallel with protection of diabetic animals against fatal shock, intestinal haemorrhage and elevation in plasma histamine levels evoked by antigen challenge. The resistance of diabetic rats to fatal shock was no longer significantly different from that of non-diabetic rats following treatment with the glucocorticoid receptor antagonist RU 486 (mifepristone). These findings indicate that endogenous glucocorticoid plays a pivotal role in the phenomenon of hyporeactivity to systemic anaphylaxis in alloxan-diabetic rats.     

甲氧氯普胺对大鼠体内萘普生钠吸收的影响

目的研究甲氧氯普胺对大鼠体内萘普生钠吸收的影响。方法将大鼠 12只分为单用组和合用甲氧氯普胺组 ,采用高效液相色谱法测定大鼠灌胃给药后不同时间点萘普生钠的血药浓度 ,并运用 3P87程序计算主要药动学参数。结果单用组和合用组的Ka 分别为 3 873h-1和 6 0 86h-1,tmax 分别为 1 0 5 2h和 0 76 8h ,cmax 分别为 0 0 95mmol/L和 0 10 7mmol/L ,AUC分别为1 4 4 5mmol·h/L和 1 881mmol·h/L。结论甲氧氯普胺可以显著缩短萘普生钠的达峰时间 ,促进药物吸收     

Differences in uptake of cadmium in selected organs of normal and alloxan-diabetic rats

The uptake of ¹⁰⁹Cd in normal and alloxan-diabetic tissues (blood, liver, kidney, pancreas, and spleen) was studied. Cadmium concentration in normal tissues, except pancreas, reached a steady state after 8 hr, whereas in alloxan-diabetic tissues, the concentration was significantly dependent on the time interval. Cadmium concentration was higher in alloxan-diabetic blood than in the blood of nondiabetic controls. Spleen uptake was higher in alloxan-diabetic tissues during the first 24 hr but not significantly different after 240 hr. Cadmium concentration was higher in alloxan-diabetic livers during the first 24 hr but was lower after 240 hr. Cadmium accumulation in kidneys was the reverse of that in liver. Pancreas uptake was lower in alloxan-diabetic tissues during the first 24 hr but not statistically different after 240 hr. It is postulated that the differences in the distribution of cadmium in control versus alloxan-diabetic rats are due mainly to diabetes, which develops due to insulin deficiency and which introduces changes in the amount of biomolecules that bind cadmium as well as in the bond strength of cadmium to the different binding sites.     

Restoration on tissue antioxidants by fenugreek seeds (Trigonella Foenum Graecum) in alloxan-diabetic rats

The influence of fenugreek seed powder supplementation in the diet on lipid peroxidation and antioxidant status was studied in normal and alloxan-diabetic rats. The protective effect of the aqueous extract of the seeds on the activity of calcium-dependent adenosinetriphosphatase (Ca2+ ATPase) in liver homogenate in the presence of Fe2+/ascorbate in vitro was also investigated. Normal and diabetic rats were provided with a diet supplemented with fenugreek seed powder for 30 days at a dosage of 2 g/kg body weight. The diabetic rats exhibited enhanced lipid peroxidation and increased susceptibility to oxidative stress associated with depletion of antioxidants in liver, kidney and pancreas. However, treatment with fenugreek seed powder normalised the alterations. In normal rats supplementation resulted in increased antioxidant status with reduction in peroxidation. Ca2+ ATPase activity in liver was protected by the aqueous extract to nearly 80% of the initial activity. The findings suggest that the soluble portion of the seeds could be responsible for the antioxidant property.     

Effects of the oral administration of a beta3-adrenergic agonist on lipid metabolism in alloxan-diabetic rats

Previous studies have reported that beta3-adrenergic agonists regulate plasma glucose, triglycerides and free fatty acids in situations of hyperglycaemia and dyslipidaemia in rodents. In this study Trecadrine, a novel compound with affinity for beta3-adrenergic receptors, has been tested in an alloxan-induced model of hyperglycaemia in rats. Alloxan-induced hyperglycaemic rats were orally treated with Trecadrine (1 mg/kg/day for 4 days), resulting in an improvement of hyperglycaemia (from 16.6 to 8.3 mmol L(-1), P < 0.001). This effect was not associated with statistical differences in plasma insulin levels, which may be explained by changes in insulin resistance and carbohydrate oxidation in peripheral tissues. Furthermore, a reduction in internal white fat weight (-39%), which was not statistically significant, as well as in plasma triglycerides (from 1.89 to 0.33 mmol L(-1), P < 0.001) and free fatty acids (from 0.70 to 0.39 mmol L(-1), P < 0.001), was found after Trecadrine administration. Trecadrine apparently induced lipolytic activity in adipocytes, as suggested by the increase of oxygen consumption in white adipose tissue (+282%, P < 0.001), while free fatty acids decreased apparently through their utilisation in other tissues. Furthermore, the increase in brown adipose tissue oxygen consumption (+50%, P < 0.01) and in rectal temperature (P < 0.05) suggests that both glucose and fatty acid oxidation may be enhanced in this tissue. These results give support to the possible therapeutic use of beta3-adrenergic compounds in situations of hyperglycaemia, particularly when this is accompanied by hypertriglyceridaemia.     

Decreased gastro-intestinal responses to certain agonists in streptozotocin- and alloxan-diabetic rats in vitro

In this study, the beta-adrenergic, muscarinic and serotonergic receptor activities were investigated in alloxan- and streptozotocin-diabetic rats using duodenum, ileum and gastric fundus strips as assay organs. In addition, the effect of manganese chloride on the duodenum of normal and diabetic rats was studied to understand whether it affects the gastro-intestinal adenylate cyclase activity. The results obtained in this study suggest that no significant changes occur in the gastro-intestinal muscarinic receptor and adenylate cyclase activities due to experimental diabetes. Nevertheless, the experiments performed on the rat duodenum and gastric fundus strips with salbutamol and serotonin showed that the beta-adrenergic and serotonergic receptor activities of the gastro-intestinal tract decreased significantly in alloxan- and streptozotocin-induced diabetes. The results obtained seem to show that the gastro-intestinal complication(s) of the diabetes were related to the reduction(s) of the beta-adrenergic and/or serotonergic receptor activities.     

Studies on the cardiovascular effects of pindolol in DOCA/saline hypertensive rats

1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 μg/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.

2 The hypotensive response and tachycardia produced by oral pindolol (50 μg/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by β-adrenoceptor stimulation.

3 After mecamylamine (10 mg/kg), oral pindolol (50 μg/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.

4 Pretreatment with oral pindolol (10 or 50 μg/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 μg/kg, orally).

5 Whereas pindolol, 50 μg/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).

6 In anaesthetized DS-rats, an equivalent degree of cardiac β-adrenoceptor blockade was produced by pretreatment with pindolol, 50 μg/kg orally (2 h previously) or intravenously (1 h previously).

7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 μg/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).

8 The hypotensive response and tachycardia produced by oral pindolol 50 μg/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.

9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral β-adrenoceptors.

     

Hemodynamic side effects of trypanocidal diamidines in rats. Studies on possible antagonisms

The influence of the alpha-receptor agonist oxymetazoline, the antihistaminics mepyramine and cimetidine and of cromoglicic acid disodium salt (disodium cromoglycate, DSCG) on the hypotension produced by the trypanocidal diamidines pentamidine, diamidinophenylindole (DAPI) and diimidazolinophenylindole (DIPI) was investigated. 75-100 nmol/kg oxymetazoline were effective only in DAPI-treated animals and diminished the drop of the systolic blood pressure by 25-49%. Pretreatment with DSCG was ineffective in all groups under the conditions used. Preapplication of a combination of 5 mumol/kg mepyramine and 10 mumol/kg cimetidine was effective only in pentamidine-treated animals and reduced the drop of the systolic pressure by 57%.     

Nanoparticle formulation increases Syzygium cumini antioxidant activity in Candida albicans-infected diabetic rats

Context: Syzygium cumini (L.) Skeels (Myrtaceae) is a medicinal plant widely used in folk medicine for the treatment of diabetes mellitus (DM). However, studies on the use of this plant and of nanoparticle formulations against DM-related fungal infections are scarce.

Objective: To evaluate the effect of the treatments with aqueous seed extract of S. cumini (ASc) and ASc-loaded polymeric nanoparticles (NPASc) on biochemical parameters in Candida albicans-infected diabetic rats.

Materials and methods: Male Wistar rats were divided into eight groups: Control, DM, C. albicans, C. albicans?+?ASc, C. albicans?+?NPASc, DM?+?C. albicans, DM?+?C. albicans?+?ASc and DM?+?C. albicans?+?NPASc. Rats were daily treated with ASc or NPASc (100?mg/kg) for 21 days. Biochemical parameters in serum and urine, advanced oxidation protein product (AOPP) and TBARS levels in the serum, kidney, liver and pancreas and N-acetyl-β-d-glucosaminidase (NAG) activities in kidney and urine were evaluated.

Results: Biochemical and oxidative stress parameters increased in rats with DM and/or candidiasis. NPASc was more effective than ASc in decreasing glucose (56%), cholesterol (33%) and creatinine (51%) levels; serum (16%) and pancreatic (46%) AOPP and renal (48%) TBARS levels when compared with DM?+?C. albicans group. In C. albicans group, both treatments decreased NAG activity but did not decrease creatinine levels.

Conclusions: These data suggest that the use of nanotechnology is able to improve plant extract properties such as antioxidant activity that may be useful in diabetes-related complications.     

Studies on sodium ion retention and antidiuretic effects after administration of l-tryptophan to rats

Summary Under certain conditions the i.p. injection of l-tryptophan leads to a reduction of elimination of Na⁺. At the same time, the fractional Na⁺-reabsorption increases. No increase in the absolute tubular sodium transport rate was observed since the significantly reduced plasma-sodium concentration leads to a decreased sodium load. The most probable cause of a decreased plasma-sodium concentration seems to be a retention of sodium-free water under the chosen conditions of infusion. The water retention is compatible with the antidiuretic effect of 5-hydroxytryptamine.